Phase I Study Assessing the Pharmacokinetic Profile, Safety, and Tolerability of a Single Dose of Ceftazidime-Avibactam in Hospitalized Pediatric Patients.

This study aimed to investigate the pharmacokinetics (PK), safety, and tolerability of a single dose of ceftazidime-avibactam in pediatric patients. A phase I, multicenter, open-label PK study was conducted in pediatric patients hospitalized with an infection and receiving systemic antibiotic therapy. Patients were enrolled into four age cohorts (cohort 1, ≥12 to <18 years; cohort 2, ≥6 to <12 years; cohort 3, ≥2 to <6 years; cohort 4, ≥3 months to <2 years). Patients received a single 2-h intravenous infusion of ceftazidime-avibactam (cohort 1, 2,000 to 500 mg; cohort 2, 2,000 to 500 mg [≥40 kg] or 50 to 12.5 mg/kg [<40 kg]; cohorts 3 and 4, 50 to 12.5 mg/kg). Blood samples were collected to describe individual PK characteristics for ceftazidime and avibactam. Population PK modeling was used to describe characteristics of ceftazidime and avibactam PK across all age groups. Safety and tolerability were assessed. Thirty-two patients received study drug. Mean plasma concentration-time curves, geometric mean maximum concentration (Cmax), and area under the concentration-time curve from time zero to infinity (AUC0-∞) were similar across all cohorts for both drugs. Six patients (18.8%) reported an adverse event, all mild or moderate in intensity. No deaths or serious adverse events occurred. The single-dose PK of ceftazidime and avibactam were comparable between each of the 4 age cohorts investigated and were broadly similar to those previously observed in adults. No new safety concerns were identified. (This study has been registered at ClinicalTrials.gov under registration no. NCT01893346.)

Higher incidence of perineal community acquired MRSA infections among toddlers

<p>Abstract</p> <p>Background</p> <p>A six-fold increase in pediatric MRSA infections, prompted us to examine the clinical profile of children with MRSA infections seen at Mercy Children's Hospital, Toledo, Ohio and to characterize the responsible strains.</p> <p>Methods</p> <p>Records were reviewed of pediatric patients who cultured positive for MRSA from June 1 to December 31, 2007. Strain typing by pulsed field gel electrophoresis (PFT) and DiversiLab, SCC<it>mec </it>typing, and PCR-based <it>lukSF-PV </it>gene (encodes Panton-Valentine leukocidin), arginine catabolic mobile element (ACME) and <it>cap</it>5 gene detection was performed.</p> <p>Results</p> <p>Chart review of 63 patients with MRSA infections revealed that 58(92%) were community acquired MRSA (CAMRSA). All CAMRSA were skin and soft tissue infections (SSTI). Twenty five (43%) patients were aged < 3 yrs, 19(33%) aged 4-12 and 14(24%) aged 13-18. Nineteen (76%) of those aged < 3 yrs had higher incidence of perineal infections compared to only 2(11%) of the 4-12 yrs and none of the 13-18 yrs of age. Infections in the extremities were more common in the older youth compared to the youngest children. Overall, there was a significant association between site of the infection and age group (Fisher's Exact p-value < 0.001). All CAMRSA were USA300 PFT, clindamycin susceptible, SCC<it>mec </it>type IVa and <it>lukSF-PV gene </it>positive. Nearly all contained ACME and about 80% were <it>cap</it>5 positive. Of the 58 USA300 strains by PFT, 55(95%) were also identified as USA300 via the automated repetitive sequence-based PCR method from DiversiLab.</p> <p>Conclusions</p> <p>CAMRSA SSTI of the perineum was significantly more common among toddlers and that of the extremities in older children. The infecting strains were all USA300 PFT. Further studies are needed to identify the unique virulence and colonization characteristics of USA300 strains in these infections.</p

Lactobacillus endocarditis with prosthetic material: a case report on non-surgical management with corresponding literature review

Lactobacilli are rod shaped gram positive bacteria that naturally colonize the human gastrointestinal and genitourinary tracts and occasionally cause disease in humans. Lactobacillus infections are found in patients who are immunocompromized or have severe comorbidities. We report Lactobacillus endocarditis in a 17-year-old adolescent girl with cardiac prosthetic material following surgical correction for complex cyanotic congenital heart disease. Accurate identification of the organism can be delayed. Despite in vivo susceptibility to vancomycin, our patient clinically failed vancomycin therapy but ultimately responded to a six-week course of penicillin, in addition to a 4-week course of clindamycin and gentamicin. She recovered without the need for surgical intervention and has been symptom free for one year. Upon review of the literature, we found that Lactobacillus endocarditis has not been reported in a pediatric patient with complex cyanotic congenital heart disease

Management of Acute Osteomyelitis: A Ten-Year Experience

Osteomyelitis is an infection of the bone; proper management requires prolonged antibiotic treatment. Controversy exists as to when a patient should transition from intravenous to oral antibiotics. However, due to the high bioavailability of some oral antibiotics, optimal time to transition from high to low bioavailability antibiotics is a more valid consideration. Additionally, there are questions surrounding the efficacy of certain antibiotics, specifically trimethoprim-sulfamethoxazole (TMP-SMX), in treating osteomyelitis. After obtaining Institutional Review Board approval from both universities, a retrospective chart review was conducted, utilizing an author-created severity scale, on all patients seen by Pediatric Infectious Diseases at the Universities of Michigan and Toledo with an acute osteomyelitis diagnosis from 2002-2012. There were 133 patients, 106 treated successfully. Success was defined in this study specifically as treatment of &lt;14 weeks without recurrence within 30 days of stopping antibiotics or permanent site disability. Seventeen patients were treated with TMP-SMX at comparable cure rates. Patients with pre-existing bone defects (noted in radiological reports), initial erythrocyte sedimentation rate (ESR) ≥70, hematogenous osteomyelitis with soft tissue extension, and skull osteomyelitis were associated with increased failure rate. Switch to low bioavailability antibiotics occurred, on average, at 3.5 weeks; however, switching before then was not associated with decreased cure rate. As prevalence of methicillin-resistant Staphylococcus aureus (MRSA), especially clindamycin- resistant MRSA, increases, TMP-SMX appears to be an acceptable antibiotic. There does not appear to be a minimum length of high bioavailability treatment required for cure. Prior bone defect, extensive infection, ESR≥70, or skull osteomyelitis may be indications for more aggressive management

Pharyngeal Colonization Dynamics of Haemophilus influenzae and Haemophilus haemolyticus in Healthy Adult Carriers▿

Haemophilus influenzae is an important cause of respiratory infections, including acute otitis media, sinusitis, and chronic bronchitis, which are preceded by asymptomatic H. influenzae colonization of the human pharynx. The aim of this study was to describe the dynamics of pharyngeal colonization by H. influenzae and an intimately related species, Haemophilus haemolyticus, in healthy adults. Throat specimens from four healthy adult carriers were screened for Haemophilus species; 860 isolates were identified as H. influenzae or H. haemolyticus based on the porphyrin test and on dependence on hemin and NAD for growth. Based on tests for hemolysis, for the presence of the 7F3 epitope of the P6 protein, and for the presence of iga in 412 of the isolates, 346 (84%) were H. influenzae, 47 (11%) were H. haemolyticus, 18 (4%) were nonhemolytic H. haemolyticus, and 1 was a variant strain. Carriers A and B were predominantly colonized with nontypeable H. influenzae, carrier C predominantly with b− H. influenzae mutants, and carrier D with H. haemolyticus. A total of 358 H. influenzae and H. haemolyticus isolates were genotyped by pulsed-field gel electrophoresis (PFGE) following SmaI or EagI digestion of their DNA, and the carriers displayed the following: carrier A had 11 unique PFGE genotypes, carrier B had 15, carrier C had 7, and carrier D had 10. Thus, adult H. influenzae and H. haemolyticus carriers are colonized with multiple unique genotypes, the colonizing strains exhibit genetic diversity, and we observed day-to-day and week-to-week variability of the genotypes. These results appear to reflect both evolutionary processes that occur among H. influenzae isolates during asymptomatic pharyngeal carriage and sample-to-sample collection bias from a large, variable population of colonizing bacteria

New simulation software to predict postoperative corneal stiffness before laser vision correction

Purpose:To develop a new virtual surgery simulation platform to predict postoperative corneal stiffness (Kcmean) after laser vision correction (LVC) surgery.Setting:Narayana Nethralaya Eye Hospital and Sankara Nethralaya, India; Humanitas Clinical and Research Center, Italy.Design:Retrospective observational case series.Methods:529 eyes from 529 patients from 3 eye centers and 10 post-small-incision lenticule extraction (SMILE) ectasia eyes were included. The software (called AcuSimX) derived the anisotropic, fibril, and extracellular matrix biomechanical properties (using finite element calculation) of the cornea using the preoperative Corvis-ST, Pentacam measurement, and inverse finite element method assuming published healthy collagen fibril orientations. Then, the software-computed postoperative Kcmean was adjusted with an artificial intelligence (AI) model (Orange AI) for measurement uncertainties. A decision tree was developed to classify ectasia from normal eyes using the software-computed and preoperative parameters.Results:In the training cohort (n = 371 eyes from 371 patients), the mean absolute error and intraclass correlation coefficient were 6.24 N/m and 0.84 (95% CI, 0.80-0.87), respectively. Similarly, in the test cohort (n = 158 eyes from 158 patients), these were 6.47 N/m and 0.84 (0.78-0.89), respectively. In the 10 ectasia eyes, the measured in vivo (74.01 [70.01-78.01]) and software-computed (74.1 [69.03-79.17]) Kcmean were not statistically different (P =.96). Although no statistically significant differences in these values were observed between the stable and ectasia groups (P =.14), the decision tree classification had an area under the receiver operating characteristic curve of 1.0.Conclusions:The new software provided an easy-to-use virtual surgery simulation platform for post-LVC corneal stiffness prediction by clinicians and was assessed in post-SMILE ectasia eyes. Further assessments with ectasia after surgeries are required